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Touch alone makes stem cells differentiate

Researchers have managed to specify the type of cell an adult stem cell will become by altering the stiffness of the material they are grown on.

Bone, nerve and muscle cell lines have been selectively initiated from human bone marrow cells by changing the physical consistency of the growth medium.

Previous studies have demonstrated that biochemical signalling strongly influences stem cell development. Now, researchers have shown for the first time that in the absence of any chemical signalling, adult bone marrow stems cells will begin to differentiate into unique cell types based solely on how tough the surrounding “tissue” is.

Adam Engler at the University of Pennsylvania, US, and colleagues isolated adult stem cells in a series of three different polymer gels, each of a different stiffness. The softest corresponded roughly to the consistency of neuronal tissue; the middle to muscle tissue; and the hardest was similar to bone.

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When undifferentiated stem cells were placed in each of the gels – devoid of any biochemical signals – they began differentiating down the path to becoming exactly the type of tissue the gels’ were designed to emulate.

Balancing act

Fully mature cells have been shown to be reliant on their physical surroundings for some time. A good example of this is fibroblasts – all-purpose mature cells found in connective tissue that can morph to form bone, cartilage, or even muscle cells.

“Cells respond extensively to their environment so this is an interesting result, but not a surprising one,” says Allan Spradling, a stem cell expert at the Carnegie Institution in Baltimore, Maryland, US. “In vivo there are many parameters to consider, and chemical signals are not insignificant. It’s probably a balancing act of all these things.”

The cells in the study expressed just the first few steps in a progression of proteins necessary for differentiation into the various cell types, and had not to matured fully.

Further work will be necessary to test whether cells can develop and form complex tissue structures without chemical signals. It also remains to be seen whether embryonic stem cells will display similar sensitivity to the mechanical properties of their surroundings.

Hard on the heart

Despite the incremental nature of the work, Engler says the study’s import lies with its implications for advancing toward a successful stem cell therapy.

When someone suffers a heart attack, for instance, cardiac muscle tissue dies and in response the body forms scar tissue, which is fibrous and harder than healthy muscle. If a doctor were to inject a patient with stem cells, Engler’s study suggests that the injected cells could form yet more scar tissue or, even worse, try and grow into bone.

“A first approach to stem cell therapies has been simply injecting cells into injured tissues,” he says. “We would say that’s not going to be sufficient because the cells would be entering an improper physical environment.”

Spradling agrees. “That has been the dominant paradigm, but it’s naïve. We need to learn how tissues repair themselves and mimic that.”